Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations. (25th March 2013)

• Record Type: Journal Article
• Authors: Charlesworth, A.; Chiaverini, C.; Chevrant‐Breton, J.; DelRio, M.; Diociaiuti, A.; Dupuis, R.P.; El Hachem, M.; Le Fiblec, B.; Sankari‐Ho, A.M.; Valhquist, A.; Wierzbicka, E.; Lacour, J.P.; Meneguzzi, G.
• Is Part Of: British journal of dermatology. Volume 168:Number 4(2013:Apr.)
• Page Start: 808
• Page End: 814
• Publication Date: 2013-03-25
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.12202
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Summary</title> <p> <bold>Background </bold> Genetic mutations in the plectin gene (<italic>PLEC</italic>) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS‐MD) or pyloric atresia (EBS‐PA). Phenotype–genotype analysis has suggested that EBS‐MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS‐PA to mutations outside this domain.</p> <p> <bold>Objectives </bold> This study aimed to describe new phenotypes of patients with EBS‐MD and EBS‐PA, to identify novel <italic>PLEC</italic> mutations and to establish genotype–phenotype correlations.</p> <p> <bold>Methods </bold> Seven patients with a suspicion of EBS linked to <italic>PLEC</italic> mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of <italic>PLEC</italic> were performed in all patients.</p> <p> <bold>Results </bold> We report the first case of nonlethal EBS‐PA improving with age, the first multisystemic involvement in a patient with lethal EBS‐PA, and the first patients with EBS‐MD with involvement of either the bladder or oesophagus. Eleven novel <italic>PLEC</italic> mutations are also reported.</p> <p> <bold>Conclusions </bold> Our results confirm that EBS‐PA is linked to mutations in the distal exons 1–30 and 32 of <italic>PLEC</italic>. Long‐term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS‐MD is linked to <italic>PLEC</italic> mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the <italic>PLEC</italic> mutation(s), but no correlation with mucosal involvement has been found.</p> </abstract>